A critical component of implantable micro-probe development and in vivo testing is the assessment of the probe in its tissue environment, which we term the morphological substrate of function. This helps to determine if the probe is causing any damage to the surrounding tissue. Just as importantly, it allows one to identify and characterize the cellular elements in the tissue that are interacting with the probe. The objectives in this project are to increase our ability to assess the interaction of the probe with its tissue substrate both in the recording mode and for stimulation. Our first objective is to further characterize the cells the probe is recording from by combining physical information with geometric information in hopes of identifying the actual cells involved in chronic recordings. For stimulation experiments, we hope to better characterize tissue reaction to the probe and to the charge flow introduced through chronic electrical stimulation. Our second objective is to generate quantitative information on cellular elements. This will allow us to characterize and compare tissue reaction with different probes and different conditions as well as to better define the normal environment the probe is operating in. Finally, our third objective is to assess and visualize in three dimensions which will support objectives on other project which involve modeling of complex patterns of tissue reaction surrounding the probe structures. All of these objectives will provide valuable feedback towards improving electrode designs.